RADIOPROTECTIVE EFFECTS OF CIMETIDINE IN MOUSE BONE-MARROW CELLS EXPOSED TO GAMMA-RAYS AS ASSAYED BY THE MICRONUCLEUS TEST

An in vivo micronucleus assay using mouse bone marrow for identifying the radioprotective effect of cimetidine is described. The influence of cimetidine, an antagonist to the histamine H2 receptor, on the kinetics of radiation-induced micronuclei was tested in the CD-1 male mouse. Cimetidine was administered at 15 mg/kg i.p.2h prior to irradiation of mouse given various doses of gamma-rays from 0.25 to 1 Gy. The frequency of micronucleated polychromatic erthyrocytes (PCEs) and normochromatic erythrocytes (NCEs) per 1500 PCEs were determined at 36, 48 and 72 h post-irradiation. The results obtained indicate a linear dose response for three sampling times, and that cimetidine reduces the number of micronuclei in both PCE and NCE at all sampling times, as well as reducing radiation cytotoxicity. When the overall effects of radiation alone or in the presence of cimetidine are compared, a dose reduction factor (DRF) of 1-5 was found for cimetidine in the dose range used in this study, which is statistically highly significant (p < 0.001). This DRF at the low dosage of cimetidine used in this study compared with known radioprotectors is very promising and it might be useful as a potent radioprotector. The mechanism by which cimetidine reduces clastogenic effects of radiation is not well understood. We propose that it might act by a radical scavenging mechanism via enzyme catalysis.